Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32585 | 97978;97979;97980 | chr2:178541324;178541323;178541322 | chr2:179406051;179406050;179406049 |
| N2AB | 30944 | 93055;93056;93057 | chr2:178541324;178541323;178541322 | chr2:179406051;179406050;179406049 |
| N2A | 30017 | 90274;90275;90276 | chr2:178541324;178541323;178541322 | chr2:179406051;179406050;179406049 |
| N2B | 23520 | 70783;70784;70785 | chr2:178541324;178541323;178541322 | chr2:179406051;179406050;179406049 |
| Novex-1 | 23645 | 71158;71159;71160 | chr2:178541324;178541323;178541322 | chr2:179406051;179406050;179406049 |
| Novex-2 | 23712 | 71359;71360;71361 | chr2:178541324;178541323;178541322 | chr2:179406051;179406050;179406049 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | None | None | 1.0 | N | 0.743 | 0.345 | 0.304108284078 | gnomAD-4.0.0 | 7.12848E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.71857E-05 |
| P/R | rs373959972  |
-0.209 | 1.0 | N | 0.854 | 0.527 | None | gnomAD-2.1.1 | 5.63E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.38E-05 | 0 |
| P/R | rs373959972 |
-0.209 | 1.0 | N | 0.854 | 0.527 | None | gnomAD-4.0.0 | 7.135E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.2889E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0975 | likely_benign | 0.0937 | benign | -1.329 | Destabilizing | 1.0 | D | 0.743 | deleterious | N | 0.465555433 | None | None | I |
| P/C | 0.5675 | likely_pathogenic | 0.553 | ambiguous | -0.946 | Destabilizing | 1.0 | D | 0.828 | deleterious | None | None | None | None | I |
| P/D | 0.8536 | likely_pathogenic | 0.8501 | pathogenic | -1.197 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | I |
| P/E | 0.6714 | likely_pathogenic | 0.6699 | pathogenic | -1.271 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| P/F | 0.5681 | likely_pathogenic | 0.5756 | pathogenic | -1.3 | Destabilizing | 1.0 | D | 0.843 | deleterious | None | None | None | None | I |
| P/G | 0.5456 | ambiguous | 0.5205 | ambiguous | -1.55 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | I |
| P/H | 0.4645 | ambiguous | 0.4731 | ambiguous | -1.008 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | I |
| P/I | 0.4289 | ambiguous | 0.4177 | ambiguous | -0.851 | Destabilizing | 1.0 | D | 0.865 | deleterious | None | None | None | None | I |
| P/K | 0.7401 | likely_pathogenic | 0.7359 | pathogenic | -1.007 | Destabilizing | 1.0 | D | 0.783 | deleterious | None | None | None | None | I |
| P/L | 0.2687 | likely_benign | 0.274 | benign | -0.851 | Destabilizing | 1.0 | D | 0.818 | deleterious | N | 0.503169522 | None | None | I |
| P/M | 0.4572 | ambiguous | 0.4494 | ambiguous | -0.604 | Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | I |
| P/N | 0.7 | likely_pathogenic | 0.6868 | pathogenic | -0.725 | Destabilizing | 1.0 | D | 0.85 | deleterious | None | None | None | None | I |
| P/Q | 0.4204 | ambiguous | 0.4114 | ambiguous | -1.034 | Destabilizing | 1.0 | D | 0.814 | deleterious | N | 0.521073194 | None | None | I |
| P/R | 0.5725 | likely_pathogenic | 0.5816 | pathogenic | -0.38 | Destabilizing | 1.0 | D | 0.854 | deleterious | N | 0.509209909 | None | None | I |
| P/S | 0.2602 | likely_benign | 0.2469 | benign | -1.171 | Destabilizing | 1.0 | D | 0.781 | deleterious | N | 0.489522265 | None | None | I |
| P/T | 0.2326 | likely_benign | 0.218 | benign | -1.15 | Destabilizing | 1.0 | D | 0.78 | deleterious | N | 0.504690459 | None | None | I |
| P/V | 0.2898 | likely_benign | 0.2817 | benign | -0.976 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
| P/W | 0.7973 | likely_pathogenic | 0.7998 | pathogenic | -1.345 | Destabilizing | 1.0 | D | 0.807 | deleterious | None | None | None | None | I |
| P/Y | 0.5968 | likely_pathogenic | 0.608 | pathogenic | -1.085 | Destabilizing | 1.0 | D | 0.854 | deleterious | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.